Changes in the optical properties of brain tissue are associated with changes in the level of neuronal activity. The method of mapping these activity-evoked optical changes is known as 'imaging of intrinsic optical signals' (IIOS), and can provide high-resolution maps of functional and pathological activity in brain tissue. Intrinsic optical signals (lOS) are thought to be generated by a combination of at least three distinct physiological mechanisms: i) changes in blood volume, ii) changes in blood oxygenation, and iii) blood-independent light scattering changes resulting from ion fluxes associated with neuronal activity. Each of these components provides important and distinct types of physiological information. IIOS has several advantages over other imaging modalities that include its relative low cost, and its unique ability to map interictal and ictal epileptiform activity with high temporal and spatial resolution. Consequently, IIOS has the potential to become a powerful tool with broad applicability in the study and treatment of epilepsy. However, IIOS has remained of limited clinical and laboratory use for at least two reasons. First, incomplete knowledge about the physiological mechanisms that generate functionally- and seizure-evoked optical changes in brain tissue limits our ability to interpret IIOS data. Second, there has been relatively little rigorous effort in determining how well IIOS data correlates spatially and temporally to functional and epileptiform neuronal activity in primates and humans. The major goals of this project are to determine the physiological mechanisms that generate normal and seizure-evoked lOS, and to establish the spatial and temporal correlates between lOS and epileptiform neuronal activity. Once these goals are achieved, the first steps will be taken to develop IIOS as a practical method for the intraoperative localization of neocortical seizure foci in adult human patients. The specific aims of this project are to: i) develop optical imaging-based spectroscopic techniques that will enable IIOS to provide high-resolution maps of changes in blood oxygenation, blood volume, and blood-independent changes in primates and human patients; ii) combine IIOS and electrophysiological studies towards gaining a more complete understanding of the links between seizure activity and the epileptiform-evoked changes in cortical hemodynamics and metabolism; and iii) apply IIOS towards the high-resolution intraoperative localization of seizure activity in human patients.